Eleanor Colle

Spontaneous diabetes mellitus syndrome in the rat. IV. Immunogenetic interactions of MHC and non-MHC components of the syndrome.

We have examined the frequency of three phenotypic characteristics of the syndrome of spontaneous diabetes (overt IDDM, lymphocytic infiltration of the pancreas, and depression of T lymphocytes) in the offspring of crosses between IDDM BB rats and rats of strains with the same and different RT1 genotypes. On the basis of these observations we propose that there are at least three components of the diabetic syndrome in the rat: (1) a requirement for the RT1u haplotype from the BB strain or a gene in close linkage with the gene coding for this haplotype, (2) a susceptibility for development of insular, periductular, or intraacinar lymphocytic infiltration in the pancreas, and (3) a susceptibility to depression of T lymphocytes. Interactions between these components as well as with other genetic and environmental factors contribute to the full expression of the syndrome.

Genetic susceptibility to the development of spontaneous insulin-dependent diabetes mellitus in the rat

Spontaneous insulin-dependent diabetes mellitus in the rat is a multigenic, multifactorial condition. We have identified three phenotypic characteristics of the syndrome. The first is an association with the RT1u haplotype of the rat major histocompatibility complex. A single RT1u haplotype is permissive, although the relative risk of developing the disease is increased when the animal is homozygous. An immunoregulatory defect, which is characterized phenotypically by a severe T lymphocyte depletion, behaves as if it were regulated by a single autosomal recessive gene which segregates independently of the RT1. The third phenotype characteristic is the presence of lymphocytic infiltration of the pancreas. The genetics of this characteristic have not been delineated, although there is evidence that it behaves as a dominant. In addition to the requirement for several genes, environmental events are important for full expression of the syndrome.

Chemical diabetes in the juvenile patient

Nine children with asymptomatic hyperglycemia have been followed for 1–712 yr with oral glucose tolerance tests and intravenous tolbutamide, glucagon, and arginine tests. Such patients are a small percentage of the total who develop overt disease. Two now receive insulin. Plasma insulin responses varied between subjects, and glucose tolerance varied between normal and abnormal in individual patients. The relationship of this disorder to typical juvenile-onset or to maturity-onset diabetes is unclear.

Dissociation of effects of somatostatin antiserum on growth hormone and insulin secretion

Growth hormone (GH) secretion in the rat is governed by an endogenous ultradian rhythm with major episodes of GH secretion occurring at approximately 3,3-hr intervals throughout a 24-hr period. Plasma GH concentrations reach levels of 400–800 ng/ml during a secretory burst and fall to undetectable levels (< 1 ng/ml) during trough periods.1 We have recently reported that the rGH secretory episodes are markedly suppressed in response to prolonged food deprivation.2 However, the mechanism of this suppression is unknown. Furthermore, the mechanism mediating the well-known suppression response of plasma insulin to starvation3 remains to be firmly established. n nSomatostatin, a tetradecapeptide originally isolated from sheep hypothalami on the basis of its ability to inhibit GH release from rat anterior pituitary cells,4 has subsequently been shown to be a potent inhibitor of both GH5–8 and insulin9–12 release in a wide variety of species. If the starvation-induced suppression of plasma GH and insulin levels is due to circulating somatostatin, we hypothesized that its effects might be neutralized or blocked by the administration of a specific antiserum to somatostatin. The aim of the experiments described in this report was to assess the role of somatostatin in mediating the inhibitory effects on GH and insulin observed during starvation.

Prolonged rupture of membranes associated with a decreased incidence of respiratory distress syndrome

The finding of an increased occurrence of prolonged ruptured membranes (ROM) in a group of prematures without RDS led to a prospective study of the effect of prolonged rupture (defined as greater than 16-hour duration) on the subsequent course of premature infants. Seventeen mother-infant pairs were included in the study and steroid determinations (total blood corticosteroids, cortisol, and corticosterone) were performed on paired maternal plasma obtained prior to delivery and infant plasma obtained within the first hour of life. There was a lower incidence of RDS in infants born after greater than 16 hours ROM (0/10), when compared to those who were born after membranes had been ruptured less than 16 hours (4/7). A correlation between steroid levels (both total blood corticosteroids and cortisol) in the infants and duration of ruptured membranes was seen. However, no correlations existed with the duration of labor. It is postulated that the protective influence which prolonged rupture of membranes imparts on the premature fetus is mediated by elevated blood corticosteroids, which result in accelerated lung maturation and a subsequent decreased incidence of respiratory distress syndrome.